Participation of Amyloid and Tau Protein in Neuronal Death and Neurodegeneration after Brain Ischemia

Abstract

Current evidence indicates that postischemic brain injury is associated with the accumulation of folding proteins, such as amyloid and tau protein, in the intra- and extracellular spaces of neuronal cells. In this review, we summarize protein changes associated with Alzheimer's disease and their gene expression (amyloid protein precursor and tau protein) after brain ischemia, and their roles in the postischemic period. Recent advances in understanding the postischemic mechanisms in development of neurodegeneration have revealed dysregulation of amyloid protein precursor, α-, β- and γ-secretase and tau protein genes. Reduced expression of the α-secretase gene after brain ischemia with recirculation causes neuronal cells to be less resistant to injury. We present the latest data that Alzheimer's disease-related proteins and their genes play a crucial role in postischemic neurodegeneration. Understanding the underlying processes of linking Alzheimer's disease-related proteins and their genes in development of postischemic neurodegeneration will provide the most significant goals to date for therapeutic development.

Keywords: amyloid; amyloid plaques; brain ischemia; dementia; genes; neurodegeneration; neurofibrillary tangles; neuronal death; presenilin; secretases; tau protein.

Figure 1

Potential role of amyloid protein precursor gene changes during brain injury due to ischemia-reperfusion. ↑-increase.

Figure 2

Potential role of tau protein gene changes during brain injury due to ischemia-reperfusion. CSF-cerebrospinal fluid, P-tau-phosphorylated tau protein, PHF-paired helical filaments, NFT-like-neurofibrillary tangle-like, NFT-neurofibrillary tangle, Glu.-glutamate, ↑-increase.